Short-term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin-sensitive ponies

Barnabé, MA; Elliott, J; Harris, PA; Menzies-Gow, NJ

Abstract

BackgroundHypoadiponectinaemia is a risk factor for endocrinopathic laminitis, but the directionality and nature of its association with insulin dysregulation is unclear.ObjectivesTo investigate the effects of short-term induced hyperinsulinaemia and dexamethasone challenge on circulating [total adiponectin] and whole blood expression of adiponectin (AdipoR1 and AdipoR2), insulin, and insulin-like growth factor 1 (IGF-1) receptors in insulin-sensitive ponies.Study designIn vivo experiment.MethodsSix never-laminitic, insulin-sensitive, native-breed UK ponies first underwent a dexamethasone challenge (0.08 mg/kg i.v.) with blood samples collected every 15 min over 3 h. After a 14-day washout period, hyperinsulinaemia was induced for 9 h via a euglycaemic-hyperinsulinaemic clamp (EHC), with blood samples collected every 30 min. Serum [insulin], plasma [total adiponectin], and plasma [IGF-1] were measured using validated assays and receptor gene expression was assessed via quantitative polymerase chain reaction (qPCR). Finally, whole blood was incubated with 10-1000 ng/mL dexamethasone for 3 h at 37 degrees C to investigate its direct effects on gene expression.ResultsThere were no adverse effects observed during either protocol. Dexamethasone challenge did not alter circulating [insulin] or [total adiponectin] at any time-point, but significantly upregulated AdipoR1 and IGF-1R expression at 150 and 180 min. Ex vivo incubation of whole blood with dexamethasone did not alter expression of the genes examined. There was no change in [total adiponectin] or expression of the genes examined associated with EHC-induced hyperinsulinemia.Main limitationsThis was a small sample size that included only native-breed ponies; total adiponectin was measured rather than high-molecular-weight adiponectin.ConclusionsShort-term induced hyperinsulinaemia and dexamethasone challenge did not affect circulating [total adiponectin] in insulin-sensitive ponies. However, dexamethasone administration was associated with upregulation of two receptors linked to adiponectin signalling, suggesting that a physiological response occurred possibly to counteract dexamethasone-associated changes in tissue insulin sensitivity.

Citation

Barnabé, M., Elliott, J., Harris, P., & Menzies-Gow, N. (2023). Short-term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin-sensitive ponies. Equine Veterinary Journal, https://doi.org/10.1111/evj.14012

• Journal Article Type: Article
• Acceptance Date: Sep 7, 2023
• Online Publication Date: Oct 6, 2023
• Publication Date: 2023
• Deposit Date: Oct 27, 2023
• Publicly Available Date: Oct 27, 2023
• Print ISSN: 0425-1644
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/evj.14012
• Keywords: adiponectin receptors; euglycaemic-hyperinsulinaemic clamp; horse; IGF-1; insulin dysregulation; insulin resistance; FACTOR-I RECEPTOR; PROLONGED HYPERINSULINEMIA; INDUCED LAMINITIS; GENE-EXPRESSION; RESISTANCE; BLOOD; PHARMACOKINETICS; MARKERS; MUSCLE; T